Anne Lynch MD, MSPH is an Assistant Professor in the Department of Obstetrics and Gynecology at the University of Colorado at Denver and Health Sciences Center (UCDHSC). Dr Lynch has an established commitment to clinical research. This Mentored Patient-Oriented Research Career Development Award will facilitate the development of Dr. Lynch into a successful independent investigator in patient-oriented research. The proposed training under the mentorship of Michael Holers MD (Immunology) Tim Byers MD, MPH (Epidemiology) and other advisors is designed to increase her skills in the area of perinatal epidmiology and immunology. This award will allow Dr. Lynch to pursue higher level epidemiology and statistical courses from the Epidemiology PhD program at UCDHSC. Classes from the UCDHSC Integrated Department of Immunology Graduate program are also included in the coursework. The objective of her research project is to study the contribution of split products from complement activation to pregnancy loss in a cohort of 1000 women. Recent studies in experimental murine models suggest that complement activation is the final effector mechanism for immunologically-mediated pregnancy loss. The proposal will translate these observations to a human study in the setting of the award. A sample for split products will be obtained from all women in the cohort in early pregnancy (<15 weeks gestation) along with a detailed clinical history. At the conclusion of the study, women with pregnancy loss will be identified from the incident cohort. The plasma samples for these women will be assayed along with those of a randomly selected comparison group of women without pregnancy loss. The levels of split products in cases will be compared to the levels in the controls. A follow-up sample will be obtained on women who suffer a loss, to evaluate for change in levels from baseline. James Muphy PhD at National Jewish Medical and Research Center will guide the univariate and multivariable logistic regression analysis of the study. This project, the mentors, the enthusiastic support from the Dept. of OB/GYN and the research resources available at UCDHSC will provide Dr Lynch with an excellent environment for her career development. The proposed study will provide unique information on the role of complement activation split products among women with pregnancy loss, and may ultimately lead to preventive treatment for this tragic outcome.